Cole Toby B, Giordano Gennaro, Co Aila L, Mohar Isaac, Kavanagh Terrance J, Costa Lucio G
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
J Toxicol. 2011;2011:157687. doi: 10.1155/2011/157687. Epub 2011 Apr 27.
Glutathione (GSH) is a major player in cellular defense against oxidative stress. Deletion of the modifier subunit of glutamate cysteine ligase (GCLM), the first and the rate-limiting enzyme in the synthesis of GSH, leads to significantly lower GSH levels in all tissues including the brain. GCLM-knockout (Gclm(-/-)) mice may thus represent a model for compromised response to oxidative stress amenable to in vitro and in vivo investigations. In order to determine whether the diminished GSH content would by itself cause behavioral alterations, a series of behavioral tests were carried out comparing young adult Gclm(-/-) with wild-type mice. Tests included the rotarod, acoustic startle reflex and prepulse inhibition of the startle reflex, open field behavior, and the platform reversal variant of the Morris Water Maze. Results showed no differences between Gclm(-/-) and wild-type mice in any of the neurobehavioral tests. However, more subtle alterations, or changes which may appear as animals age, cannot be excluded.
谷胱甘肽（GSH）是细胞抵御氧化应激的主要成分。谷氨酸半胱氨酸连接酶（GCLM）的修饰亚基缺失，GSH合成过程中的首个限速酶，会导致包括大脑在内的所有组织中的GSH水平显著降低。因此，GCLM基因敲除（Gclm(-/-)）小鼠可能代表了一种对氧化应激反应受损的模型，适用于体外和体内研究。为了确定GSH含量的减少本身是否会导致行为改变，我们进行了一系列行为测试，比较了年轻成年Gclm(-/-)小鼠和野生型小鼠。测试包括转棒试验、听觉惊吓反射和惊吓反射的前脉冲抑制、旷场行为以及莫里斯水迷宫的平台反转变体。结果显示，在任何神经行为测试中，Gclm(-/-)小鼠和野生型小鼠之间均无差异。然而，不能排除更细微的改变，或随着动物年龄增长可能出现的变化。
